Etiology

Fever in a patient with neutropenia may be caused by a bacterial, viral, or fungal infection. Of these, bacterial bloodstream infections are the most commonly identified infectious etiology in cancer patients with febrile neutropenia, and may result in significant mortality.[19][20][21][22][23]​​​​​​​​​[24] Host endogenous flora is often the primary source of causative pathogens.[23][25]​​​​​[26]​​[27]

Contemporary data indicate that gram-negative organisms may be isolated more frequently than gram-positive organisms, likely due to increasing antibiotic resistance.[28]​​ The most common gram-negative organisms include Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa. The most common gram-positive organisms include coagulase-negative staphylococci, Staphylococcus aureus, and Enterococcus species.[28] With the advent of advanced molecular techniques for microbial identification, it is anticipated that there will be an increase in reporting of microbiologically defined anaerobic bloodstream infections.[29]

Viral pathogens isolated from patients with febrile neutropenia include respiratory viruses, Epstein-Barr virus, and human herpesvirus 6.[24][30]

Fungi (predominantly Candida and Aspergillus species) are found in 2% to 10% of at-risk patients, particularly in those with concomitant corticosteroid use, those who are older, and those with relapsed or refractory hematologic malignancy.[3][31]​​​ Importantly, the use of antifungal prophylaxis during the neutropenic period in certain high-risk populations has had a significant impact on reducing risk for fungal infection.[32]

Pathophysiology

Patients receiving cytotoxic chemotherapy may develop neutropenia, which predisposes to infection.[33] Chemotherapy-induced myelosuppression is often the main mechanism driving neutropenia. Radiation therapy can also cause or contribute to neutropenia by direct radiation damage to dividing myeloid stem and progenitor cells.

Mucosal breaches are an important route of entry for bacteria. This may occur due to damage of the endothelial lining caused by chemotherapy or radiation therapy (i.e., mucositis), and subsequent translocation of endogenous flora across the mucosa and into the bloodstream.[34] Bacteria or fungi (e.g., Candida) may enter the bloodstream via indwelling catheters or implanted devices that have been colonized by endogenous flora, or from contamination during insertion or manipulation.

Patients with hematologic malignancies may have immune dysfunction affecting both innate and adaptive immunity, allowing infections to progress unopposed. In patients with leukemia or lymphoma, immune dysfunction may be related to leukopenia (e.g., resulting from abnormal hematopoiesis and bone marrow dysfunction), hypogammaglobulinemia, qualitative defects in neutrophil function (e.g., impaired chemotaxis and phagocytosis), and/or defective cell-mediated immunity. The degree and type of immune defect(s) is a major predictor of risk for infection, with neutropenia classically a risk for bacterial and/or fungal infection, and concomitant defects in cell-mediated immunity (often related to chemotherapy) representing risk for fungal and/or viral infection.

Use of this content is subject to our disclaimer